Impact of Bisphenol A on neural stem cells and development in the adult brain

描述（由申请人提供）：双酚A （BPA）是世界上最普遍的化学制品之一。它是一种具有雌激素效应的有机化合物，用于生产塑料复合材料和环氧树脂，这些材料用于制造食品容器、牙科产品、热收据纸以及我们日常遇到的许多其他物品。由于BPA在我们的环境和生态系统中无处不在，因此了解偶然接触BPA的生理影响至关重要。本研究的目的是关注成熟的中枢神经系统，并确定BPA在成人大脑中神经干细胞和神经元发育中的作用。成人神经可塑性的一个最显著的例子是大脑齿状回中神经元的从头形成

DESCRIPTION (provided by applicant): Bisphenol A (BPA) is one of the most prevalent manufactured chemicals in the world. An organic compound with estrogenic effects, it is used in the production of plastic composites and epoxy resins that are used to make food containers, dental products, thermal receipt paper, and many other items that we encounter on a daily basis. Because of its pervasive presence in our environment and ecosystem, it is critical that we understand the physiological effects of our incidental contact with BPA. The objective in this proposal is to focus on the mature central nervous system and identify the role of BPA on neural stem cells and neuronal development in the adult brain. One of the most striking examples of adult neural plasticity is the de novo formation of neurons throughout life in the dentate gyrus of the hippocampus. Convergent data suggests that this phenomenon plays a critical role in cognition and the regulation of affective behavior. Many of these functional roles appear to be part of a feedback loop in which environmental factors can alter the levels of adult neurogenesis, which in turn may alter our ability to cope with environmental demands. It is therefore paramount that one identifies the nature and mechanisms underlying the interaction between this form of adult neural plasticity and the environment. One such area in need of systematic investigation is the neural impact of frequently encountered environmental chemicals. To begin to address this gap in knowledge, the focus here is on BPA as an entry point for a rigorous analysis of how a near ubiquitous chemical contaminant may affect the activation and fate choice of neural stem cells and the development of their neuronal progeny. To accomplish this objective, novel quantitative approaches developed and refined in this laboratory will be used to analyze how BPA may regulate stem cell behavior and the properties of newborn neurons in the adult hippocampus. Taking advantage of a recently developed "clonal analysis" approach, both the identifying and quantifying properties of individual stem cells and stem cell populations in the adult brain following systemic exposure to BPA will be tested (Specific Aim 1). Further quantification of the impact of BPA on the developmental trajectory of newborn neurons will be accomplished using retroviral-mediated fluorescent labeling to enable morphological and electrophysiological analyses (Specific Aim 2). The results of these experiments should provide critical new information on the potential health risks of exposure to BPA and its effect on the adult central nervous system. PUBLIC HEALTH RELEVANCE: BPA is one of the most prevalent chemicals in our environment but there are little data on its effect on the adult central nervous system. Our proposed experiments will provide critical new information regarding the effect of BPA on neural stem cells and development in the adult brain and provide a foundation for future regulatory evaluation of this chemical.